Clinical features of pulmonary arterial hypertension associated with systemic sclerosis

Abstract

Systemic sclerosis is an autoimmune disorder of the connective tissue characterized by disordered inflammation and fibrosis leading to skin thickening and visceral organ complications. Pulmonary involvement, in the form of pulmonary arterial hypertension and/or interstitial lung disease, is the leading cause of morbidity and mortality among individuals with scleroderma. There are no disease-specific therapies for pulmonary involvement of scleroderma, and pulmonary arterial hypertension in this cohort has typically been associated with worse outcomes and less clinical response to modern therapy compared to other forms of Group I pulmonary hypertension in the classification from the World Symposium on Pulmonary Hypertension. Ongoing research aims to delineate how pathologic microvascular remodeling and fibrosis contribute to this poor response and offer a window into future therapeutic targets.

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again

“…There are three primary vasodilatory pathways of interest in PAH: the nitric oxide (NO) pathway, endothelin (ET) pathway, and prostacyclin pathway. To date, drugs for SSc-PAH primarily act through these three pathways, and drugs targeting these three pathways have been shown to relieve PAH-associated symptoms [1,121]. In PH, pulmonary arterial endothelial cells (PAECs) regulate the contractile and diastolic function of vessels by secreting contractile factors such as thromboxane A2 (TXA 2 ) and endothelin-1 (ET-1) as well as diastolic factors such as PGI 2 and nitric oxide (NO) [122].…”

“…Systemic sclerosis (SSc) is a heterogeneous autoimmune disorder characterized by chronic inflammation, endothelial dysfunction, and fibrosis of the skin and internal organs [1]. The prevalence of SSc worldwide is approximately 176 cases per one million population with the annual incidence of 14 cases per one million person-year [2].…”

“…The prevalence of SSc worldwide is approximately 176 cases per one million population with the annual incidence of 14 cases per one million person-year [2]. SSc affects women more frequently than men with a 3-4:1 female:male ratio; however, men with SSc experience more severe outcomes [1].…”